Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4S45WJ)

• DOT Name: Bridging integrator 2 (BIN2)
• Synonyms: Breast cancer-associated protein 1
• Gene Name: BIN2
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Neurofibromatosis type 2
• UniProt ID: BIN2_HUMAN
• PDB ID: 4AVM; 4I1Q
• Pfam ID: PF03114 ; PF21532
• Sequence:
  MAEGKAGGAAGLFAKQVQKKFSRAQEKVLQKLGKAVETKDERFEQSASNFYQQQAEGHKL
  YKDLKNFLSAVKVMHESSKRVSETLQEIYSSEWDGHEELKAIVWNNDLLWEDYEEKLADQ
  AVRTMEIYVAQFSEIKERIAKRGRKLVDYDSARHHLEAVQNAKKKDEAKTAKAEEEFNKA
  QTVFEDLNQELLEELPILYNSRIGCYVTIFQNISNLRDVFYREMSKLNHNLYEVMSKLEK
  QHSNKVFVVKGLSSSSRRSLVISPPVRTATVSSPLTSPTSPSTLSLKSESESVSATEDLA
  PDAAQGEDNSEIKELLEEEEIEKEGSEASSSEEDEPLPACNGPAQAQPSPTTERAKSQEE
  VLPSSTTPSPGGALSPSGQPSSSATEVVLRTRTASEGSEQPKKRASIQRTSAPPSRPPPP
  RATASPRPSSGNIPSSPTASGGGSPTSPRASLGTGTASPRTSLEVSPNPEPPEKPVRTPE
  AKENENIHNQNPEELCTSPTLMTSQVASEPGEAKKMEDKEKDNKLISANSSEGQDQLQVS
  MVPENNNLTAPEPQEEVSTSENPQL
• Function: Promotes cell motility and migration, probably via its interaction with the cell membrane and with podosome proteins that mediate interaction with the cytoskeleton. Modulates membrane curvature and mediates membrane tubulation. Plays a role in podosome formation. Inhibits phagocytosis.
• Tissue Specificity: Detected in natural killer cells (at protein level). Highest level expression seen in spleen and peripheral blood leukocytes and is also expressed at high levels in thymus, colon and placenta, suggesting preferential expression in hematopoietic tissues.
• Reactome Pathway:
  Signaling by membrane-tethered fusions of PDGFRA or PDGFRB (R-HSA-9673768)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Neurofibromatosis type 2	DISI8ECS	Limited	Biomarker	[3]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Bridging integrator 2 (BIN2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Bridging integrator 2 (BIN2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Bridging integrator 2 (BIN2).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Bridging integrator 2 (BIN2).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Bridging integrator 2 (BIN2).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Bridging integrator 2 (BIN2).	[9]

References

• [1] A genome-wide association study of aging.Neurobiol Aging. 2011 Nov;32(11):2109.e15-28. doi: 10.1016/j.neurobiolaging.2011.05.026. Epub 2011 Jul 22.
• [2] Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation.Sci Rep. 2017 Dec 19;7(1):17762. doi: 10.1038/s41598-017-17999-3.
• [3] Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.Oncol Lett. 2018 May;15(5):6825-6830. doi: 10.3892/ol.2018.8225. Epub 2018 Mar 9.
• [4] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.